Non-Alcoholic Fatty Liver Disease: non-invasive diagnosis with MR Elastography and MR Spectroscopy

Non-alcoholic fatty liver disease (NAFLD) is the term for the spectrum of liver
disease that ranges from simple steatosis (accumulation of triglycerides in the
liver) to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. NASH is a
more serious, inflammatory condition in which progressive fibrosis can lead to
cirrhosis. NAFLD is related to the etiological features of obesity, type II
diabetes and dyslipidemia (metabolic syndrome). The growing epidemic of obesity
has led to an increased prevalence of NAFLD, affecting up to 30% of the general
population in various countries. This prevalence is expected to rise even
further. A progression of liver fibrosis is observed in 37% of patients with
NALFD/NASH, and mortality of patients with NASH is significantly higher than in
patients with simple steatosis without fibrosis. Therefore, the identification
of liver fibrosis in patients with NAFLD/NASH is essential for the prognosis of
disease progression. To date, liver biopsy is still the gold standard for the
diagnosis of NASH. Liver biopsy, however, has a number of limitations. Firstly,
it is an invasive procedure accompanied by the risk of complications and
patient discomfort and is therefore not suitable for screening or treatment
evaluation. Secondly, biopsy has a poor reproducibility, due to heterogeneous
distribution of liver fibrosis, the small size of the samples (approximately
1/50,000 of the total liver parenchyma) and the inter- and intra-observer
variability in the histological examination by a pathologist. Therefore, a
non-invasive alternative is needed to diagnose and stage NAFLD and to
distinguish NASH from simple steatosis without fibrosis.

Magnetic Resonance Elastography (MRE) has been introduced as an accurate
non-invasive method to determine liver fibrosis. MRE provides reproducible,
three dimensional viscoelastic information of the whole liver, and is not prone
to sampling errors. The findings of MRE have been studied in a wide spectrum of
chronic liver diseases.

Proton Magnetic Resonance Spectroscopy (1H-MRS) can accurately and reproducibly
measure the accumulation of fat in the liver, a key component of NAFLD. 1H-MRS
is a safe, non-invasive, non-ionizing diagnostic tool that enables the
quantitative evaluation of lipid contents by measuring the signal of hydrogen
atoms both in water and in the fatty acid chains.

A recent animal study suggested that MRE could be useful in the early detection
of NASH. In this animal study, two rat models for NAFLD were used: A model
representing simple steatosis and a model representing NASH. Elasticity and
viscosity parameters of the liver in both models, using MRE, were compared with
control rats. In the NASH model, both viscosity and elasticity parameters were
significantly higher than those of the control rats. In the simple steatosis
model, however, only viscosity was significantly higher, whereas the elasticity
was not significantly higher compared with controls.

From these results, we hypothesize that MRE, in combination with 1H-MRS might
be a potential powerful diagnostic method to distinguish NASH from simple
steatosis in NAFLD. This hypothesis has, however, not been studied yet.

Primary Objective:
* The feasibility of combining MRE and 1H-MRS in NAFLD to distinguish simple
steatosis from NASH.

Secondary Objective(s):
* The influence of steatosis on MRE measurement
* The influence of inflammation on MRE measurement

This is a single centre, non-randomized observational cohort study.

Participating in this study leads to no immediate advantage for the individual
patient. However, it is important to understand the underlying mechanisms of
NAFLD and NASH for the patient group as a whole. Therefore an accurate
non-invasive diagnostic tool is mandatory. We expect MRE in combination with
1H-MRS to be a superior tool in diagnosing and monitoring NALFD and NASH.
Therefore in the future, patients with NAFLD and NASH can benefit considerably
by this new diagnostic modality.

MR Elastography and proton MR Spectroscopy (1H-MRS) will be performed during
one MRI session of approximately 30-40 minutes. Both MRE and 1H-MRS are
non-invasive, non-ionizing examinations, during which the patient will have to
lie still on his back in a MRI scanner. No contrast medium will be
administered. Participating in the study will require either one extra visit to
the hospital. Patients are not delayed in treatment for their disease. There
will be little extra physical and psychological discomfort associated with
participation.

Travelling expenses will be refunded.